Glucocorticoids are potent anti-inflammatory agents inhibiting cytokine production and lymphocyte trafficking. The molecular mechanism for steroid suppression is not well characterized, but associated with activation of steroid receptors. Glucocorticoid potentially blocks both activation and placement of lymphocytes throughout the body. Cytokines regulate a balance between lymphocyte proliferation due to activation and cell losses due to apoptosis to establish the total number of T cells in the body. Chemokines direct lymphocytes distribution between secondary immune organs and tertiary tissues by controlling the migration through the blood and lymphatics. Lymphocyte distribution is controlled by passage into or out of the circulation, processes regulated by the surface expression E-selectin and ICAM-1. Elevated levels of cortisol causes two suppressing events: reduced levels of circulating CD4+ and CD8+ lymphocytes, and a loss of E-selectins and ICAM-1 on cultured epithelial cells. Both findings appear contradictory: if extravasation is blocked, then the number of CD4+ and CD8+ cells should remain constant, or increase in the circulation. In addition, endogenous glucocorticoids do not cause permanent immunosuppression, thus arguing against apoptosis causing a loss of T cells. The following specific aims will determine how the lymphocyte trafficking pattern is altered by glucocorticoids: 1) does dexamethasone alter adhesion molecule expression on lymphocyte or vascular endothelium; and 2) does dexamethasone alter the transition from naive T cell to effector T cell. I will use adoptive transfers to isolate and fluorescently label lymphocytes from a donor mouse for tracking movement in a second host mouse. Lymphocytes will be quantitated using flow cytometry, and fluorescently labeled MHC ll-tetramers will track the development of an antigen specific response. Glucocorticoids are potent immunosuppressive agents associated with stress responses. Elevated glucocorticoid levels resulting from severe acute stress or from chronic conditions such as mood disorders have been correlated to the appearance of chronic infectious disease and autoimmune disorders. This study will determine if glucocorticoids do alter in vivo T cell function. [unreadable] [unreadable] [unreadable]